NR ABXJ
AU Bruce,M.E.; McBride,P.A.; Jeffrey,M.J.; Scott,J.R.
TI PrP in pathology and pathogenesis in scrapie-infected mice
QU Molecular Neurobiology 1994 Apr-Jun; 8(2-3): 105-12
PT journal article
AB PrP accumulation in the brains of mice infected with scrapie takes several different forms: amyloid plaques, widespread accumulation in neuropile, and perineuronal deposits. PrP is also sometimes detected within microglia and in or around astrocytes. There are dramatic and reproducible differences between scrapie strains in the relative prominence of these changes and their distribution in the brain. Depending on the scrapie strain, PrP pathology is targeted precisely to particular brain areas, often showing a clear association with identifiable groups of neurons. These results suggest that PrP changes are primarily associated with neurons, and that different scrapie strains recognize and selectively replicate in different populations of neurons. Immunostaining at the ultrastructural level demonstrates an association of PrP with neurite plasmalemma, around amyloid plaques, and in areas of widespread neuropile and perineuronal accumulation. It is probable that PrP is encoded by the Sinc gene, which controls the incubation period of scrapie in mice. Studies using the intraocular infection route show that the Sinc gene controls the onset rather than the rate of replication, suggesting that PrP may be involved in cell-to-cell spread of infection. The accumulation of PrP at the surface of neurons is consistent with such a role.
IN In scrapieinfizierten Mausgehirnen wurden verschiedene Formen der Prionproteinakkumulation beobachtet. Neben amyloiden Plaques gibt es eine weit verbreitete Akkumulation in Nervenfortsätzen sowie perineuronale Ablagerungen. Das Prionprotein wird an neuronalen Zellmembranen und manchmal auch in Mikroglia sowie in und um Astrozyten gefunden. Die Anteile dieser Formen an der Prionproteinakkumulation und ihre Verteilung im Gehirn sind sehr unterschiedlich und sollen vom infizierenden Scrapiestamm abhängen. Jeder Erregertyp scheint bestimmte Gruppen von Neuronen zu bevorzugen und sich nur an diesen zu vermehren. Die Autoren halten es für wahrscheinlich, dass das Prionprotein vom Sine-Gen kodiert wird, welches bei Mäusen die Inkubationszeit beeinflußt. Studien mit einer Infektion von Mäusen durch die Augen sollen gezeigt haben, dass das Sinc-Gen eher den Beginn als die Rate der Vermehrung veränderter Prionproteine beeinflußt.
ZR 23
MH Animal; Astrocytes/metabolism/pathology; Brain/metabolism/*pathology; Hippocampus/metabolism/pathology; Immunohistochemistry; Mice; Mice, Inbred C57BL; Microglia/metabolism/pathology; Microscopy, Immunoelectron; Neurons/metabolism/*pathology/ultrastructure; Organ Specificity; Prions/analysis/*metabolism; Scrapie/*pathology/*physiopathology
AD
Moira E. Bruce (moira.bruce@bbsrc.ac.uk), Patricia A. McBride (tricia.mcbride@bbsrc.ac.uk), Institute for Animal Health, BBSRC and MRC, Neuropathogenesis Unit, Ogston Building, West Mains Road, Edinburgh EH9 3JF, Scotland, UK; Martin J. Jeffrey (m.jeffrey@vla.maff.gov.uk), VLA Lasswade Veterinary Laboratory, Pentlands Science Park, Bush Loan, Penicuik, Edinburgh EH26 OPZ, Scotland, UK
IAH AFRC & MRC Neuropathogenesis Unit, Edinburgh, UK
SP englisch
PO USA